典型文献
Bmal1 inhibits phenotypic transformation of hepatic stellate cells in liver fibrosis via IDH1/α-KG-mediated glycolysis
文献摘要：
Hepatic stellate cells(HSCs)play an important role in the initiation and development of liver fibrogenesis,and abnormal glucose metabolism is increasingly being considered a crucial factor controlling phenotypic transformation in HSCs.However,the role of the factors affecting glycolysis in HSCs in the experimental models of liver fibrosis has not been completely elucidated.In this study,we showed that glycolysis was significantly enhanced,while the expression of brain and muscle arnt-like protein-1(Bmal1)was downregulated in fibrotic liver tissues of mice,primary HSCs,and transforming growth factor-β1(TGF-β1)-induced LX2 cells.Overexpression of Bmal1 in TGF-β1-induced LX2 cells blocked glycolysis and inhibited the proliferation and phenotypic transformation of activated HSCs.We further confirmed the protective effect of Bmal1 in liver fibrosis by overexpressing Bmal1 from hepatic adeno-associated virus 8 in mice.In addition,we also showed that the regulation of glycolysis by Bmal1 is mediated by the isocitrate dehydrogenase 1/α-ketoglutarate(IDH1/α-KG)pathway.Collectively,our results indicated that a novel Bmal1-IDH1/α-KG axis may be involved in regulating glycolysis of activated HSCs and might hence be used as a therapeutic target for alleviating liver fibrosis.
文献关键词：
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作者姓名：
Lei Xu;Tian-yu Yang;Yi-wen Zhou;Mei-fei Wu;Jie Shen;Jie-ling Cheng;Qing-xue Liu;Shi-yang Cao;Jian-qing Wang;Lei Zhang
作者机构：
School of Pharmacy,Anhui Medical University,Hefei 230032,China;Inflammation and Immune Mediated Diseases Laboratory of Anhui Province,Hefei 230032,China;The Key Laboratory of Anti-inflammatory and Immune Medicines,Ministry of Education,Hefei 230032,China;The Fourth Affiliated Hospital of Anhui Medical University,Hefei 230032,China
文献出处：
引用格式：
[1]Lei Xu;Tian-yu Yang;Yi-wen Zhou;Mei-fei Wu;Jie Shen;Jie-ling Cheng;Qing-xue Liu;Shi-yang Cao;Jian-qing Wang;Lei Zhang-.Bmal1 inhibits phenotypic transformation of hepatic stellate cells in liver fibrosis via IDH1/α-KG-mediated glycolysis)[J].中国药理学报（英文版）,2022(02):316-329
A类：
B类：
Bmal1,inhibits,phenotypic,transformation,hepatic,stellate,cells,liver,fibrosis,IDH1,KG,mediated,glycolysis,Hepatic,HSCs,play,important,role,initiation,development,fibrogenesis,abnormal,glucose,metabolism,increasingly,being,considered,crucial,controlling,However,factors,affecting,experimental,models,has,been,completely,elucidated,In,this,study,showed,that,was,significantly,enhanced,while,brain,muscle,arnt,like,protein,downregulated,fibrotic,tissues,mice,primary,transforming,growth,TGF,induced,LX2,Overexpression,blocked,inhibited,proliferation,activated,We,further,confirmed,protective,effect,by,overexpressing,from,adeno,associated,virus,addition,also,regulation,isocitrate,dehydrogenase,ketoglutarate,pathway,Collectively,our,results,indicated,novel,axis,may,involved,regulating,might,hence,used,therapeutic,target,alleviating
AB值：
0.552298
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